Cancer is a worldwide major public health concern. In 2020, the American Cancer Society reported that more than 600,000 cancer deaths are predicted in the United States (https://www.cancer.org/). Inflammation, a fundamental innate immune response, is considered a hallmark of cancer given its tight association with several essential processes associated with tumor growth (Coussens & Werb, 2002; Crusz & Balkwill, 2015). Inflammation is caused by multiple stimuli such as injury, toxins, infections, smoke, UV radiation, and obesity. Under physiological conditions, inflammation is suppressed by a programmed resolution (Sugimoto, Sousa, Pinho, Perretti, & Teixeira, 2016). Paradoxically, inflammation is also involved in multiple pathophysiological processes, especially in the different stages of tumor development, including initiation, promotion, and progression (Coussens & Werb, 2002; Crusz & Balkwill, 2015). Several malignancies arise from damaged tissue at sites of persistent infection, which causes chronic inflammation. This leads to the production of several inflammatory chemokines and cytokines, such as TNF-α, MCP-1/CCL2, IL-6, and CXC motif chemokine ligand 12 (CXCL12)/Stromal cell-derived factor- 1 (SDF-1), as well as mediators, such as lipid metabolites from fatty acids. However, given the insufficient production of anti-inflammatory mediators during this process, cell proliferation in the damaged tissue is stimulated, facilitating mutagenesis, tumorigenesis, and tumor cell invasiveness (Greten & Grivennikov, 2019; Savant, 2018; Turner, Nedjai, Hurst, & Pennington, 2014). In addition to the molecular evidence that inflammation is associated with cancer, clinical data, such as the high prevalence of cancer (e.g., colon, lung, and prostate cancers) in patients with inflammatory colitis, bronchitis, and prostatitis, respectively, supports the link between inflammation and cancer (Lutgens et al., 2008: Platz & De Marzo, 2004; Singh et al., 2019). Therefore, modulation of inflammatory pathways may be an effective approach for the development of cancer therapies.

Among lipid mediators produced under inflammation stimuli, eicosanoids are a class of functionally active lipid products derived from dietary polyunsaturated fatty acids, most frequently arachidonic acid (AA). They are mainly produced by a series of enzymatic pathways that include cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 epoxygenase (CYP450), as shown in Fig. 1. Alternatively, a small proportion of eicosanoids result from auto-oxidation of AA. Eicosanoids comprise at least several hundred individual molecules, including leukotrienes, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and hydroperoxyeicosatetraenoic acids (HpETEs), some of which remain to be fully characterized. They play an important role in the inflammatory response and in inflammation-related cancers, as demonstrated by reports showing that inhibiting either COX or LOX pathways reduces the development of several cancers (Orafaie et al., 2020).

Given the diversity of lipid metabolites, eicosanoids exert a wide range of biological functions (Table 2, Table 3). Research focused on the specific function of each lipid metabolite is key to unravel how these molecules might be used in the development of anti-cancer agents. In this review, we focus on the activities and the potential molecular mechanisms associated with AA-derived eicosanoids, as well as their role in inflammation and cancer development, to explore potential anti-cancer agents.